TRPM4 (transient receptor potential cation channel subfamily M member 4)

Gene

• Entrez ID: 54795
• Gene name: Transient receptor potential cation channel subfamily M member 4
• Gene symbol: TRPM4
• Synonyms (NCBI Gene): EKVP6, LTrpC4, PFHB1B, TRPM4B, hTRPM4
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs71352737	G>A	Benign, likely-pathogenic	Intron variant, coding sequence variant, stop gained
rs140799936	A>G,T	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, stop gained, coding sequence variant
rs141531245	C>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, 5 prime UTR variant, coding sequence variant, synonymous variant, intron variant
rs144781529	A>G	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, genic upstream transcript variant, coding sequence variant, upstream transcript variant, intron variant
rs145501662	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, 5 prime UTR variant, genic upstream transcript variant, coding sequence variant, upstream transcript variant, intron variant
rs148763371	T>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, 5 prime UTR variant, intron variant, coding sequence variant
rs148855956	C>T	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Genic upstream transcript variant, coding sequence variant, upstream transcript variant, stop gained, intron variant
rs172151858	A>G	Pathogenic	Missense variant, coding sequence variant
rs200038418	G>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant, intron variant
rs200132598	G>A	Likely-pathogenic, uncertain-significance	Splice donor variant, intron variant
rs267607142	G>A	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs387907216	C>T	Pathogenic	Coding sequence variant, upstream transcript variant, 5 prime UTR variant, genic upstream transcript variant, missense variant, intron variant
rs1278993777	C>G,T	Pathogenic	Coding sequence variant, synonymous variant, missense variant
rs1369949906	T>C	Pathogenic	Missense variant, coding sequence variant
rs1425995839	G>T	Likely-pathogenic	Coding sequence variant, genic upstream transcript variant, intron variant, stop gained, upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017409	hsa-miR-335-5p	Microarray	18185580
MIRT023660	hsa-miR-1-3p	Microarray	18668037
MIRT1457324	hsa-miR-3616-5p	CLIP-seq
MIRT1457325	hsa-miR-3647-5p	CLIP-seq
MIRT1457326	hsa-miR-4279	CLIP-seq
MIRT1457327	hsa-miR-4488	CLIP-seq
MIRT1457328	hsa-miR-4635	CLIP-seq
MIRT1457329	hsa-miR-4697-5p	CLIP-seq
MIRT1457330	hsa-miR-573	CLIP-seq
MIRT2137137	hsa-miR-3184	CLIP-seq
MIRT2137138	hsa-miR-339-5p	CLIP-seq
MIRT2137139	hsa-miR-423-5p	CLIP-seq
MIRT2137140	hsa-miR-4281	CLIP-seq
MIRT2357945	hsa-miR-3136-3p	CLIP-seq
MIRT2357946	hsa-miR-3677-5p	CLIP-seq
MIRT2357947	hsa-miR-4645-3p	CLIP-seq
MIRT2357948	hsa-miR-663b	CLIP-seq
MIRT2137137	hsa-miR-3184	CLIP-seq
MIRT2137139	hsa-miR-423-5p	CLIP-seq
MIRT2137140	hsa-miR-4281	CLIP-seq
MIRT2396385	hsa-miR-4481	CLIP-seq
MIRT2396386	hsa-miR-4710	CLIP-seq
MIRT2396387	hsa-miR-4745-5p	CLIP-seq
MIRT2396388	hsa-miR-4758-5p	CLIP-seq
MIRT2396389	hsa-miR-4792	CLIP-seq
MIRT2651473	hsa-miR-1915	CLIP-seq
MIRT2651474	hsa-miR-3199	CLIP-seq
MIRT2651475	hsa-miR-4505	CLIP-seq
MIRT2651476	hsa-miR-4515	CLIP-seq
MIRT2651477	hsa-miR-4726-3p	CLIP-seq
MIRT2651478	hsa-miR-640	CLIP-seq
MIRT2651473	hsa-miR-1915	CLIP-seq
MIRT2651474	hsa-miR-3199	CLIP-seq
MIRT2651475	hsa-miR-4505	CLIP-seq
MIRT2651476	hsa-miR-4515	CLIP-seq
MIRT2651477	hsa-miR-4726-3p	CLIP-seq
MIRT2651478	hsa-miR-640	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002250	Process	Adaptive immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002407	Process	Dendritic cell chemotaxis	IEA
GO:0002407	Process	Dendritic cell chemotaxis	ISS
GO:0002724	Process	Regulation of T cell cytokine production	IDA	20656926
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005227	Function	Calcium-activated cation channel activity	IBA
GO:0005227	Function	Calcium-activated cation channel activity	IDA	27207958, 29211723
GO:0005227	Function	Calcium-activated cation channel activity	IEA
GO:0005227	Function	Calcium-activated cation channel activity	ISS
GO:0005262	Function	Calcium channel activity	IEA
GO:0005272	Function	Sodium channel activity	TAS
GO:0005509	Function	Calcium ion binding	IDA	29217581
GO:0005515	Function	Protein binding	IPI	31837246
GO:0005516	Function	Calmodulin binding	IEA
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005783	Component	Endoplasmic reticulum	IDA	19945433
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005794	Component	Golgi apparatus	IDA	19945433
GO:0005794	Component	Golgi apparatus	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	19945433, 29211723
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006816	Process	Calcium ion transport	IEA
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	ISS
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	20625999
GO:0010460	Process	Positive regulation of heart rate	ISS
GO:0016020	Component	Membrane	IDA	29217581
GO:0016020	Component	Membrane	IEA
GO:0016925	Process	Protein sumoylation	IDA	19726882
GO:0019722	Process	Calcium-mediated signaling	IDA	27207958
GO:0030001	Process	Metal ion transport	IBA
GO:0030502	Process	Negative regulation of bone mineralization	ISS
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034706	Component	Sodium channel complex	IDA	27207958
GO:0035774	Process	Positive regulation of insulin secretion involved in cellular response to glucose stimulus	ISS
GO:0042802	Function	Identical protein binding	IPI	29211723, 29217581
GO:0043025	Component	Neuronal cell body	ISS
GO:0045600	Process	Positive regulation of fat cell differentiation	ISS
GO:0045668	Process	Negative regulation of osteoblast differentiation	ISS
GO:0045907	Process	Positive regulation of vasoconstriction	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0046873	Function	Metal ion transmembrane transporter activity	IEA
GO:0051289	Process	Protein homotetramerization	IDA	29211723, 29217581
GO:0051289	Process	Protein homotetramerization	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070588	Process	Calcium ion transmembrane transport	IEA
GO:0070588	Process	Calcium ion transmembrane transport	TAS
GO:0071318	Process	Cellular response to ATP	IEA
GO:0086045	Process	Membrane depolarization during AV node cell action potential	IMP	27207958
GO:0086047	Process	Membrane depolarization during Purkinje myocyte cell action potential	IMP	27207958
GO:0086048	Process	Membrane depolarization during bundle of His cell action potential	IMP	27207958
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IMP	27207958
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IDA	20625999
GO:0098655	Process	Monoatomic cation transmembrane transport	IBA
GO:0098662	Process	Inorganic cation transmembrane transport	IDA	29211723
GO:0098662	Process	Inorganic cation transmembrane transport	IEA
GO:0098719	Process	Sodium ion import across plasma membrane	IDA	27207958
GO:0098911	Process	Regulation of ventricular cardiac muscle cell action potential	IMP	27207958
GO:1903949	Process	Positive regulation of atrial cardiac muscle cell action potential	ISS
GO:1904179	Process	Positive regulation of adipose tissue development	ISS
GO:1904199	Process	Positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization	ISS

Other IDs

• MIM: 606936
• HGNC: 17993
• e!Ensembl: ENSG00000130529

Protein

• UniProt ID: Q8TD43
• Protein name: Transient receptor potential cation channel subfamily M member 4 (hTRPM4) (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (Melastatin-4)
• Protein function: Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellular Ca(2+), it is impermeable to it (PubMed:120
• PDB: 5WP6, 6BQR, 6BQV, 6BWI, 8RCR, 8RCU, 8RD9, 9B8W, 9B8X, 9B8Y, 9B8Z, 9B90, 9B91, 9B92, 9B93, 9B94
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18139	LSDAT_euk	88 → 355	SLOG in TRPM	Family
  PF00520	Ion_trans	786 → 1055	Ion transport protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed with a high expression in intestine and prostate. In brain, it is both expressed in whole cerebral arteries and isolated vascular smooth muscle cells. Prominently expressed in Purkinje fibers. Expressed at higher level
• Sequence:

  MVVPEKEQSWIPKIFKKKTCTTFIVDSTDPGGTLCQCGRPRTAHPAVAMEDAFGAAVVTV
  WDSDAHTTEKPTDAYGELDFTGAGRKHSNFLRLSDRTDPAAVYSLVTRTWGFRAPNLVVS
  VLGGSGGPVLQTWLQDLLRRGLVRAAQSTGAWIVTGGLHTGIGRHVGVAVRDHQMASTGG
  TKVVAMGVAPWGVVRNRDTLINPKGSFPARYRWRGDPEDGVQFPLDYNYSAFFLVDDGTH
  GCLGGENRFRLRLESYISQQKTGVGGTGIDIPVLLLLIDGDEKMLTRIENATQAQLPCLL
  VAGSGGAADCLAETLEDTLAPGSGGARQGEARDRIRRFFPKGDLEVLQAQVERIMTRKEL
  LTVYSSEDGSEEFETIVLKALVKACGSSEASAYLDELRLAVAWNRVDIAQSELFRGDIQW
  RSFHLEASLMDALLNDRPEFVRLLISHGLSLGHFLTPMRLAQLYSAAPSNSLIRNLLDQA
  SHSAGTKAPALKGGAAELRPPDVGHVLRMLLGKMCAPRYPSGGAWDPHPGQGFGESMYLL
  SDKATSPLSLDAGLGQAPWSDLLLWALLLNRAQMAMYFWEMGSNAVSSALGACLLLRVMA
  RLEPDAEEAARRKDLAFKFEGMGVDLFGECYRSSEVRAARLLLRRCPLWGDATCLQLAMQ
  ADARAFFAQDGVQSLLTQKWWGDMASTTPIWALVLAFFCPPLIYTRLITFRKSEEEPTRE
  ELEFDMDSVINGEGPVGTADPAEKTPLGVPRQSGRPGCCGGRCGGRRCLRRWFHFWGAPV
  TIFMGNVVSYLLFLLLFSRVLLVDFQPAPPGSLELLLYFWAFTLLCEELRQGLSGGGGSL
  ASGGPGPGHASLSQRLRLYLADSWNQCDLVALTCFLLGVGCRLTPGLYHLGRTVLCIDFM
  VFTVRLLHIFTVNKQLGPKIVIVSKMMKDVFFFLFFLGVWLVAYGVATEGLLRPRDSDFP
  SILRRVFYRPYLQIFGQIPQEDMDVALMEHSNCSSEPGFWAHPPGAQAGTCVSQYANWLV
  VLLLVIFLLVANILLVNLLIAMFSYTFGKVQGNSDLYWKAQRYRLIREFHSRPALAPPFI
  VISHLRLLLRQLCRRPRSPQPSSPALEHFRVYLSKEAERKLLTWESVHKENFLLARARDK
  RESDSERLKRTSQKVDLALKQLGHIREYEQRLKVLEREVQQCSRVLGWVAEALSRSALLP
  PGGPPPPDLPGSKD

• Sequence length: 1214

Pathways

KEGG:

Insulin secretion

Reactome:

TRP channels

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Associated diseases

Causal
Disease merge term	Disease name	dbSNP ID	References
Erythrokeratoderma	Erythrokeratodermia variabilis et progressiva 6	rs1278993777	N/A
Heart Block	Progressive familial heart block type IB	rs267607142, rs172151858	N/A

Unknown
Disease merge term	Disease name	Evidence	References	Source
Alzheimer disease	Alzheimer's disease or family history of Alzheimer's disease	N/A	N/A	GWAS
arrhythmogenic right ventricular cardiomyopathy	Arrhythmogenic right ventricular cardiomyopathy	N/A	N/A	ClinVar
Brugada Syndrome	brugada syndrome	N/A	N/A	ClinVar
cardiomyopathy	Cardiomyopathy	N/A	N/A	ClinVar
Catecholaminergic Polymorphic Ventricular Tachycardia	Catecholaminergic polymorphic ventricular tachycardia 1	N/A	N/A	ClinVar
Conduction Disorder Of The Heart	conduction disorder of the heart	N/A	N/A	ClinVar
Hypertrophic cardiomyopathy	hypertrophic cardiomyopathy	N/A	N/A	ClinVar
Long QT Syndrome	long qt syndrome	N/A	N/A	ClinVar
Short QT Syndrome	short qt syndrome	N/A	N/A	ClinVar
Ventricular Fibrillation	ventricular fibrillation	N/A	N/A	ClinVar
ventricular tachycardia	Ventricular tachycardia	N/A	N/A	ClinVar
Wolff-Parkinson-White Syndrome	Wolff-Parkinson-White pattern	N/A	N/A	ClinVar

Associations from Text Mining
Disease Name	Relationship Type	References
Andersen Syndrome	Associate	28315637
Arrhythmias Cardiac	Associate	35500522, 38467355
Arrhythmogenic Right Ventricular Dysplasia	Associate	33922380
Atrial Fibrillation	Stimulate	28839241
Atrioventricular Block	Associate	27207958, 33959666, 35205305, 36352534
Autoimmune Diseases of the Nervous System	Associate	39546944
Brain Edema	Associate	30484364, 35474489, 39189437
Brain Injuries Traumatic	Associate	30484364, 34309670, 37037835
Breast Neoplasms	Associate	32484822
Brugada Syndrome	Associate	23382873, 27207958, 36352534, 38100498
Bundle Branch Block	Associate	23382873
Cardiac Conduction System Disease	Associate	33594499
Cardiomyopathy Dilated	Associate	28750076
Central Nervous System Diseases	Associate	39227362
Colorectal Neoplasms	Associate	31441200, 35500522
Colorectal Neoplasms	Inhibit	36147460
Congenital heart block	Associate	19726882
Deafness	Associate	26636822
Death Sudden	Associate	33895855
Disease Progression	Associate	35205305
Endometrial Neoplasms	Associate	34936030, 36231119
Epileptic Syndromes	Associate	35205305
Fatigue Syndrome Chronic	Associate	27834303
Genetic Diseases Inborn	Associate	38100498
Heart Block	Associate	23382873
Heart Diseases	Associate	26636822, 27207958, 31441200, 32037394, 32529721, 35205305, 38100498, 39546944
Heart Failure	Stimulate	33594499
Heart Failure	Associate	33594499
Heart Valve Diseases	Associate	40194969
Heat Stress Disorders	Associate	39457051
Hereditary bundle branch system defect	Associate	19726882, 38100498
Hypertrophy	Associate	33594499
Hypoplastic Left Heart Syndrome	Associate	32037394
Immune System Diseases	Associate	31441200, 35500522
Inflammation	Associate	37037835
Intracranial Hypertension	Associate	30484364, 34309670
Long QT Syndrome	Associate	28315637, 33466149, 36010573, 36352534
Lymphedema	Associate	27207958
Myopathy Central Core	Associate	26636822
Neoplasm Metastasis	Inhibit	36147460
Neoplasms	Associate	26496025, 31441200, 32484822, 35500522, 39546944
Neoplasms	Inhibit	36147460
Neurologic Manifestations	Associate	30484364
Prostatic Intraepithelial Neoplasia	Stimulate	26496025
Prostatic Neoplasms	Stimulate	26496025, 26590985
Prostatic Neoplasms	Associate	28614631, 31441200, 33058873
Sepsis	Associate	39227362
Sudden Infant Death	Associate	35474489
Timothy syndrome	Associate	28315637
Virus Diseases	Associate	39227362